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Report: RESVERATROL 2012 2^nd International Conference of Resveratrol and Health (December 8, Leicester, England)

“Committee:  a group of men who individually can do nothing, but as a group decide that nothing can be done.”

A collaborative group of scientific investigators, resveratrol raw-material manufacturers and branders of commercially available resveratrol-based products met in Leicester, England to chart the future direction for this miraculous natural molecule.  The group covered a broad range of disorders that resveratrol addresses, which includes aging and cancer as well as important other issues such as optimal dosing and models for testing.  Their full report can be read online here.

While the group concluded there is not unequivocal scientific data to support resveratrol for disease prevention in humans (OK for lab mice however) or human life extension (the only way to conclusively show resveratrol extends human life is to conduct a 99-year study), it did say there are encouraging preliminary results.

The group concluded that “there is not yet sufficient evidence to unequivocally support a therapeutic effect of resveratrol for the treatment of any specific conditions,” but failed to mention that the FDA is blocking any such efforts by declaring a New Drug Application must be filed to conduct a study that addresses any human disease.  So there is no way to proceed in studying human disease as long as research institutions rely upon the FDA’s review board.

Currently, resveratrol products are exclusively available as dietary supplements, not as drugs.  Supplements are limited to making structure and function claims, such as “supports a healthy heart” and cannot claim they prevent, treat or cure any disease.

The only resveratrol-based drug company (Sirtris Pharmaceuticals) was purchased by GlaxoSmithKline (GSK) for $720 million in 2008 and GSK subsequently abandoned further research and development after overdosing terminal cancer patients on resveratrol, which resulted in kidney failure.

The report mentions that the same formula of resveratrol made by Sirtris/GSK was used among healthy individuals without harm, so there would be no reason for GSK to abandon research other than to keep it off the market.  Resveratrol poses a major threat to modern pharmacology as it would theoretically replace many prescription drugs currently on the market.

The dose makes the poison

While the report did say there were conflicting reports over the effectiveness of resveratrol, it failed to address the problem of overdosing which turns resveratrol from being an antioxidant cell protector into a promoter of oxidation that is cell-killing (cytotoxic).   Pro-oxidant doses would only be appropriate for killing cancer cells or pathogenic germs.

No mention was made of hormesis, which is defined as a mild biological toxin that activates natural internal antioxidant defenses.  Low-dose resveratrol is often panned as a hormesis agent.  Mega-dose resveratrol would negate any hormetic effect.  The failure of a number of animal and human studies could be attributed to overdosing and makes one think researchers are intentionally scuttling resveratrol’s future.

Mega-doses ill advised

While there are an estimated 413 brands of resveratrol-based products on the market today, resveratrol is offered in a wide dosage range, starting at 25 to 1000 milligrams.  The working group report appeared to give license to using up to 2000 mg of resveratrol.

It is true that no deaths or serious adverse reactions have been reported for resveratrol-based products over the past 8 years since most of these products were first introduced, however provision of resveratrol in gram doses (1000 mg) appears to be imprudent.

One animal study showed that the human equivalent of 1750-3500 mg of resveratrol actually increased the area of damage to hearts in the animal laboratory that were subjected to an experimentally-induced heart attack.  Gene activation studies show relatively low-dose resveratrol can mimic the gene expression observed in calorie restricted animals.

This writer warns that resveratrol primarily chelates copper which is required for synthesis of collagen in the body and resveratrol exhibits anti-growth properties that would make it inappropriate for growing children and menstruating and child-bearing females.

Frontal headaches and fatigue are not uncommon among young menstruating females who try resveratrol pills.  Anemic or mega-dose users may experience Achilles heel soreness (tendonitis) which is believed to be caused by a shortage of copper for collagen synthesis.

Mistaken lack of bioavailability

The report made no mention of bioavailability of resveratrol.  Studies show about 70% of resveratrol is orally absorbed and then it is shuttled to the liver where it is conjugated (attached) to detoxification molecules (glucuronate, sulfate) which render it non-bioavailable (too large to pass through cell walls).  Many mistaken researchers maintain resveratrol is not bioavailable for this very reason.  But the molecule is working in human eyes, hearts and other remote organs, so it must be biologically active.

Researchers fail to recognize that at the site of inflammation, infection or malignancy an unzipping enzyme (glucuronidase) is up to 20-fold more active and releases resveratrol as a free unbound molecule.  This is known as nature’s drug delivery system.  Resveratrol is most certainly bioavailable at the right time and place.

This is important to recognize since a newly launched study using mega-dose resveratrol among patients with early-stage Alzheimer’s disease has just been launched.  Mistakenly assuming resveratrol is not bioavailable, this study is designed to provide 1000-2000 milligrams of resveratrol to elderly subjects, many whom are taking prescription drugs for other conditions.  There may be drug-herb reactions and at this dose, and mega-dose resveratrol promotes oxidation.

The aged subjects in this study are known to often have weak fragile capillaries in the brain where mega-doses of resveratrol could pose problems.  This mega-dose study could end up dooming resveratrol forever should it report serious side effects.  Resveratrol could be likened to the horrific side effects caused by thalidomide.  Confronted about potential over-dosing problems, the lead investigator for this study defended high-dose resveratrol over alleged issues involving bioavailability.

Resveratrol-drug interactions not addressed

The working group made no mention of resveratrol and biochemical incompatibility with prescription drugs.  Resveratrol inhibits detoxification (cytochrome p450) enzymes in the liver which dull the effects of Rx drugs.  If drugs are taken at the same time as resveratrol, the drug may work too strongly.  This would be of concern if patients are taking blood thinners or blood pressure-lowering medications.

Some patients taking resveratrol with their blood pressure pills have reported transient dizziness.  Fortunately, this problem is self-limiting as resveratrol is completely metabolized in the liver within minutes of consumption and any side effects would be transient.  But it would be wise to take resveratrol 2-4 hours apart from medicines.

Lab rats rejoice!

Unexpectedly, the resveratrol working group concluded that there IS sufficient evidence for “chemopreventive effects of resveratrol on the development of cancer in mouse skin” and there are “promising results on the prevention of colon and prostate cancer in animals.”

Foot-dragging by modern medicine

While the working group concluded there is sufficient evidence to suggest resveratrol “enhances vascular health and reduces hypertension, heart failure and ischemic (oxygen-starvation) heart disease in experimental animal models,” the report failed to mention that there has not been a single human clinical study launched for heart or artery disease in the past 8 years.  Modern medicine is dragging its feet here.

Another oversight: cardiac preconditioning

A bevy of researchers report resveratrol “preconditions” the heart prior to a heart attack, which is considered the most preferential way to avert mortal heart attacks.  The heart produces protective antioxidants (superoxide dismutase, catalase, glutathione, heme oxygenase, adenosine) immediately following a heart attack.  However, resveratrol is perceived by the body as a mild biological stressor.  Therefore, resveratrol activates these internal antioxidants prior to a heart attack, thus limiting any damage to heart muscle should a heart attack occur.  The working group made no mention of resveratrol in the prevention of sudden-mortal heart attacks.

Many gene targets but no aim

The working committee went on to say that while resveratrol has many gene targets, “there is not sufficient evidence to link a specific gene target to a specific health benefit.”

However, a microRNA study conducted by National Institutes of Health researchers showed that resveratrol, and more so resveratrol + other small molecules (Longevinex®), inhibits genes that control vascular endothelial growth (VEGF), a protein that activates new blood vessels in oxygen-starved tissues.

In a small number of cases, a resveratrol-based supplement has been shown to cause abnormal blood vessels at the back of human eyes to recede and vision to be rapidly restored.  The resveratrol-based pill (Longevinex®) used was shown to exhibit six-fold greater anti-VEGF effect than plain resveratrol and is limited to use when other prescription anti-VEGF injected medicines fail to work.  So here may be an example of a commercially available resveratrol pill out-performing a modern medicine.

Sad and mistaken conclusions

Sadly, due to foot-dragging by the research community, the working group had to conclude that “published evidence from human trials is not sufficiently strong to justify the recommendation of chronic resveratrol consumption by humans for any given indication.”  The problem is, the questions over effectiveness is likely years away from being answered at the slow speed the research community is moving.

The report said “the use of resveratrol is not an alternative to maintaining a healthy lifestyle,” yet that is the very thing it was first showcased for – that the red-wine drinking French eating a high-cholesterol, high-fat diet don’t experience anywhere near the same coronary artery disease mortality as North Americans (known as the French Paradox).  Red wine is the most potent natural source of resveratrol.

The bigger problem is that even the best science may not increase public demand for resveratrol.  The herbal pine bark extract marketed under the trade name Pycnogenol has over 200 positive published studies yet it is mired as a lowly-selling dietary supplement.  Will that be the same fate for resveratrol?  A leading supplier of synthetic resveratrol recently abandoned production, a sign that resveratrol’s future is still up in the air.  © 2013 Bill Sardi, ResveratrolNews.com